Human leprosy presents itself as a spectrum of disease syndrome with the tuberculoid form at one pole and lepromatous form at the other. Similar variability in the nature of this disease occurs when mice are infected with different species of mycobacteria. Infection of mice with a small inoculum of the human pathogen, Mycobacterium leprae, results in a limited localized growth of the bacilli without any systemic involvement. Infection of the same strain of mouse with the murine pathogen, Mycobacterium lepraemurine (MLM), results in the development of a disease that in many ways resembles human leprosy. Cell-mediated immunity (CMI) is implicated as responsible for limiting the growth of M. leprae in mouse footpads, but the evidence is not conclusive. The experiments proposed in this application will make use of powerful tool of adoptive immunization technique in conjunction with other manifestations of CMI to analyze the cellular or humoral basis of immunity to M. leprae. The properties of this acquired immunity will be compared with the response that is associated with a progressive infection of mice with MLM. There is enough evidence that CMI is generated in MLM-infected mice, but not sustained in face of progressive infection. Thus, these hosts are not genetically unresponsive to MLM, but suffer from a specific acquired suppression of CMI. This will be investigated as a model system to study the immunoregulatory mechanisms using anti R1Rv immunity as a measure of protective (cross-reactive) immunity and cell-surface alloantigen markers as a probe.